tbuckley/cabot-search huggingface dataset:
Abstract 15424: The Toxic Tango: Tyrosine Kinase Inhibitors (TKI) and Immune Checkpoint Inhibitors (ICI) Toxicities
Authors: Juan D Del Cid Fratti, Rimmy Garg, Carlos Requeña, Chetan Bhardwaj
Journal: Circulation (2022)

Introduction: ICI and TKI have several cardiotoxicity side effects. We present a case of TKI-ICI toxicity resulting in multiorgan inflammatory syndrome with myocarditis and thrombotic STEMI that was treated with high-dose steroids and PCI. Case Presentation: 72-year-old man presented with acute SOB and inferior STEMI. He complains of severe DOE for the past 3 months, chronic diarrhea, and altered mental status. PMH of renal cell carcinoma (RCC) limited to kidney s/p nephrectomy. Follow-up CT scan with 4cm inferior left adrenal gland mass avid for FDG-PET and IR-biopsy positive for RCC. He was started on Pembrolizumab 200mg IV q3 weeks and axitinib 5mg PO q12h for the past 5 months. Investigation: LHC showed a thrombotic lesion in RCA with normal rest of coronaries without evidence of atherosclerosis or bystander plaque with successful PCI-DES. TTE with inferior wall hypokinesis and moderate pericardial effusion with organized material. Elevated CRP/ESR. Despite PCI, he is unable to walk 200ft due to DOE and needs supplemental O2. VQ scan low % for PE, PFT mild obstructive disease with severe reduction DLCO, and HRCT moderate emphysema, bronchial/ septal thickening, and normal hemodynamics in RHC. CMR demonstrated moderate pericardial effusion with internal debris, LVEF 38%, myocardial edema, and delayed gadolinium enhancement from base to apical inferior wall. Treatment: Empirical trial of IV-methylprednisolone 500mg IV q12 was started with drastic improvement of shortness of breath, resolution of AMS, ESR/CRP, and discontinuation of oxygen. Follow-up TTE with normal LVEF and resolution of pericardial effusion. Conclusions: ICI-Myocarditis is a severe irAE. The diagnosis requires clinical suspicion and exclusion of other cardiac conditions due to the high fatality rate. Early recognition and prompt treatment are needed to improve mortality. TKI-related arterial-thromboembolic events is not common but if present different therapy options should be offered.
Abstract 15699: High-Dose Anthracycline Administration and Development of Cardiotoxicity in Women With Breast Cancer: An Analysis of Real-World Data From a Nationwide Claims Database in Japan
Authors: Hiroshi Ohtsu, Akihiko Shimomura, Sakiko Miyazaki, Shinichiro Ueda, Naohiro Yonemoto, Chikako Shimizu, Kazuhiro Sase
Journal: Circulation (2022)

Introduction: Breast cancer is the most common malignancy affecting women, and the number of survivors is increasing with the advent of new therapies. However, Anthracyclines (ACs) retain an essential role in the drug treatment of breast cancer, despite their known cardiotoxicity. Although dexrazoxane, a cardioprotective agent for high-dose AC administration, has been approved in the US and Europe, it remains one of the drug-lag issues in Japan. Objective: To evaluate real-world data on the proportion of high-dose anthracycline administration and the incidence of cardiotoxicity in Japanese patients with breast cancer using a nationwide claims database. Methods. This study is a retrospective observational analysis using the Japan Medical Data Centre (JMDC, Tokyo, Japan) database, an anonymized patient-level claims database younger than 75 years old. We first identified women diagnosed with breast cancer and treatment with AC. Patients with a history of heart failure and a treatment start record of fewer than six months were excluded. After adjusting for patient background factors by propensity score matching (PSM), cardiotoxicity risk factors and outcomes were compared between the high-dose group (AC-H) and the low-dose group (AC-L). Results: Among women with breast cancer who underwent AC treatment between January 2015 and September 2020, 5.3% (255/4,831) were classified to the high-dose group. After PSM, the number of cases, age (years) and follow-up (months) in each group were as follows: AC-H group (n=254, median 51.0 [IQR: 46.0-55.0], 26.0 [14.0-52.0]), AC-L group (n=254, 51.0 [46.0-57.0], 32.5 [15.0-59.0]). The 5-year rates of mortality and heart failure in AC-H and AC-L groups were 33.1% vs 4.5% (Log-rank p &amp;lt; .0001) and 11.0% vs 4.3% (Log-rank p=0.003), respectively. Conclusion: The proportion of women with breast cancer who received AC in the high dose group was approximately 5%. However, compared with the low-dose group, the high-dose group had a lower survival rate and a higher incidence of heart failure. Therefore, in Japan, clinical development of cardioprotective agents for patients with metastatic or recurrent breast cancer who require high doses of AC is warranted.
Abstract 15906: The Role of Different Anticoagulants in the Setting of Heart Failure With Preserved Ejection Fraction (hfpef) and Atrial Fibrillation
Authors: Rand Ibrahim, Mario Mekhael, Chan Ho Lim, Lilas Dagher, Nour Chouman, Abdel Hadi El Hajjar, Charbel Noujaim, Nassir Marrouche
Journal: Circulation (2022)

Introduction: The prediction of morbidity and mortality by various anticoagulants in the setting of AF has been well described, its relevance has not been investigated in the subset of patients with HFpEF. We sought to delineate the effect that different anticoagulation regimens (DOACs vs warfarin) carry on the risk of ischemic strokes and death in AF and HFpEF. Methods: The ReachNet national registry for Medicare patients was used. The diagnosis of AF was determined using ICD-9 and ICD-10 codes. A total of 737 patients who had AF had a diagnosis of HFpEF. Survival analyses were conducted to predict time-to-stroke and time to death. The role of different anticoagulants was then assessed using Cox-regression analysis while adjusting for covariates (age, sex, BMI, smoking, HT, DM, CAD, history of malignancy). Results: The cohort (58.6% males) had an average age of 65 ± 10 years. Comorbidities included HTN (80%), DM (50%), CAD (48%), history of ischemic stroke (5%), and obesity (51%). Of patients on anticoagulation, the majority were on warfarin (51.4%) with the remaining 48.6% on DOACs. Median time to stroke formation was 18 ± 2 months, while that for all-cause mortality was 10 ± 2 months. Females had significantly higher incidences of stroke (OR=6.7, p&lt;0.01). Additionally, patients receiving DOACs were 3.7 times more likely to experience stroke (p&lt;0.01), but anticoagulation regimen did not predict mortality in logistic regression analysis. Cox-regression analysis assessing incidence of ischemic stroke revealed no difference between the different anticoagulation regimens (HR=0.243). In the prediction of all-cause mortality, however, the use of DOACs was associated with a 15-fold increased risk of death compared to the use of warfarin alone (p&lt;0.001). Conclusions: AF patients suffering from HFpEF are a vulnerable population at great risk of ischemic strokes and a short life expectancy. Although unadjusted analysis predicts a higher incidence of strokes with the use of DOACs, this did not translate to the prediction of strokes in the long-term. All-cause mortality, however, seems to be reduced to a great extent in the setting of long-term warfarin administration.
Abstract 219: Cerebral Oximetry Shows The Cardiopulmonary Resuscitation Leading To Return Of Spontaneous Circulation
Authors: Ruth Salaberria, ANDIMA LARREA REDIN, ELISABETE ARAMENDI, Zoraida Cabezas, Edurne M Mugica, Ander Arnedo
Journal: Circulation (2022)

Purpose: Effectiveness of cardiopulmonary resuscitation (CPR) is associated to return of spontaneous circulation (ROSC), but the alignment of the characteristics of compressions (rate and depth) to AHA recommendations has not been proven to improve outcome. In this study the power of the near infrared spectroscopy to discriminate productive CPR, i.e. chest compression sequences leading to ROSC, was evaluated. Material and methods: The cerebral oxygen saturation (rSO 2 ) measured in both cerebral lobules was recorded with the Nonin SenSmart 100X oximeter by Emergentziak-Osakidetza, the emergency service of the Basque Country, in the out-of-hospital cardiac arrest (OHCA). Concurrently, the ECG and bioimpedance were recorded by the Lifepak 15 desfibrillator. Chest compressions were delivered by Lucas 2 &amp; Lucas 3 devices. Sequences of compressions longer than 30 s were extracted, and changes in the left (rSO 2,L ) and right (rSO 2,R ) lobes were automatically computed by signal processing. The increase of rSO2, measured every 4 s during the CPR-sequence, was adjusted with linear regression and compared for ROSC/no-ROSC patients as registered in the emergency department (ED). Results: Chest compression intervals were identified in the bioimpedance, and 403 CPR-segments were extracted from 115 patients (80 from 43 patients with ED-ROSC) with a mean(std) duration of 2.46(1.07) min. The median(IQR) increase of brain saturation per patient, rSO 2,L and rSO 2,R , were 2.1(1.1-5.5) and 1.9(0.9-3.8) points. The figure shows the linear adjustment of the evolutions for both ROSC/no-ROSC groups, with slopes of: 1.81 vs 1.23 min -1 for ΔrSO 2,L (p&gt;0.05), 1.78 vs 0.95 min -1 (p&lt;0.05) for ΔrSO 2,R, and 2.03 vs 1-08 min -1 (p&lt;0.05) for the combination of both. Conclusions: Cerebral oximetry showed different evolution during mechanical chest compressions for patients with ED-ROSC. Significantly higher slopes in the rSO 2 evolution were observed for patients who achieved ROSC in OHCA.
Abstract 251: Brain Computed Tomography After In-Hospital Cardiac Arrest
Authors: Cecelia R Ratay, Clifton W Callaway, Jonathan Elmer, Kate Flickinger, Patrick J Coppler
Journal: Circulation (2022)

Background: Brain computed tomography (CT) is useful to identify early cerebral edema after cardiac arrest and neurological causes arrest. Most early CT data come from out-of-hospital cardiac arrest (OHCA). The prevalence of edema and neurological causes of arrest is unknown after in-hospital cardiac arrest (IHCA). Purpose: To compare the frequency of edema and neurologic causes of arrest after IHCA and OHCA. Methods: We identified patients treated at a single medical center between January 2010 and August 2020 who had a brain CT within 24 hours of arrest. We abstracted age, sex, initial cardiac rhythm, duration of arrest, and survival to hospital discharge in all patients, and cause of death in decedents. We measured grey to white matter ratio (GWR) at the level of the basal ganglia. We categorized GWR as normal (1.30), mild edema (&gt;1.20 and &lt;1.30), and severe (1.20). We compared age, duration of arrest, GWR and edema category by arrest location using Wilcoxon-Rank-Sum and Fisher’s Exact tests. Results: Of 2,413 subjects (464 (19%) IHCA and 1949 (81%) OHCA), 1,725 had a brain CT within 24 hours of collapse (IHCA n=157, 9%; OHCA n=1,568, 91%) and were included. Subjects who suffered IHCA were significantly older (median 64 [interquartile range (IQR) 54 - 74] years vs 59 [IQR 49-70] years), had shorter CPR durations (IHCA median 10 [IQR 5-18] vs OHCA median 21 [IQR 13 - 34], p &lt;0.001) and higher GWR (IHCA median 1.33 [1.29 - 1.41], OHCA median 1.3 [1.20 - 1.36], p&lt;0.001). Severe edema was less common in IHCA (n=8, 5%) than OHCA (n=270, 24%). Mild edema was common after IHCA (n=49, 32%). Few CT scans revealed a neurological etiology of arrest (IHCA n=3, 2%; OHCA n=63, 4%). In-hospital death increased with edema, (no edema, n=48, 50%; mild, n=36, 73%; severe, n=8, 100%). Among deaths, 50% were attributed to perceived poor neurological prognosis. Conclusions: While severe edema is not as common as after OHCA, mild edema is relatively common after IHCA. Preventing and treating cerebral edema is important for survivors of IHCA.
Abstract 177: Optimal Selection Of Predictors To Enhance Prognostic Performance In Post-resuscitation Care: A Single Center Experience
Authors: Bong kyu Lee, Yeonho You, Jung Soo Park, Jin Hong Min, Yong Nam In, Changshin Kang
Journal: Circulation (2022)

Objectives: The aim of this study was to investigate the optimal combinations that would enhance prognostic accuracy in post-resuscitation care after out-of-hospital cardiac arrest (OHCA). Methods: Prospectively registry data collected between May 2018 and January 2022 were analyzed. We analyzed the prognostic performance of all single predictors suggested from current guidelines: no ocular reflexes (OR) at 72 h, highly malignant pattern in electroencephalography at ≥ 24 h, neuron-specific enolase (NSE) at 72 h, and diffuse anoxic injury at 72 h on image studies of computed tomography (CT) and diffusion-weighted image (DWI). Gray-to-white matter ratio and high-signal intensity on CT and DWI, respectively, were used as a tool to estimate abnormal findings. We also analyzed the prognostic accuracy of combining strategies using 2 to 3 abnormal results from predictors. All prognostic accuracies were analyzed as sensitivities with false positive ratios (FPR) of &lt; 2%. The primary outcome was poor neurological outcome after 3 months from OHCA. Results: We assessed 119 comatose adult survivors of OHCA, of whom 62 (52.1%) had poor neurological outcomes. The highest sensitivity among single prognostic modalities was found in abnormal DWI, with an FPR of &lt; 2% (86.3%, 95% confidence interval [CI] 73.7 - 94.3). In multimodal assessments, combining NSE and DWI (87.8%, 95% CI 75.2 - 95.4) and combining NSE, OR, and DWI (87.8%, 95% CI 75.2 - 95.4) showed the highest sensitivities in dual and triple combining prognostic strategies, respectively. Combining strategies with image study at 72 h, regardless of whether CT or DWI, improved the sensitivities of every non-imaging study modality. Conclusions: This study emphasizes that combining prognostic strategies for multimodal assessment can enhance prognostic reliability. In particular, this combining strategy, along with the image study at 72 h, can be valuable to ensure the reliability of prognostication in post-resusciation care. 1
Abstract 214: A Counterfactual Machine Learning Model Study To Estimate The Impact Of Coronary Angiography For Out Of Hospital Cardiac Arrest
Authors: Yasuhito Kawagoe, Makoto Nishimori, Soshiro Ogata, Masakazu Shinohara, Yoshihiro J Akashi, Yoshio Tahara
Journal: Circulation (2022)

Background: The American Heart Association guidelines for resuscitation 2020 recommends emergency coronary angiography (CAG) in cases of out-of-hospital cardiac arrest (OHCA) after return of spontaneous circulation (ROSC) with ST-segment elevation(STE) and, it is unclear how much CAG actually contributes to improved outcomes in various OHCA patient populations. The aim of this study is to estimate the impact of CAG on OHCA using a counterfactual machine learning model. Methods: We analyzed adult non-traumatic OHCA patients (43,977 cases) from June 2014 to December 2019 from the JAAM (Japan Association for Acute Medicine)-OHCA registry, which includes post-hospitalization data from 140 Japanese hospitals. We defined outcomes as favorable neurological outcomes (Cerebral Performance Categories (CPC) 1-2) and survival at 30 and 90 days. We estimated the outcome assuming that all patients had received CAG using a machine learning and counterfactual hypothetical model, and also estimated the outcome assuming that all patients had not received CAG. An average of each individual difference between the two estimations was calculated as average treatment effect (ATE) (%), which represents the effect of CAG on improving outcomes for the population. In addition, subgroup analysis was performed based on ROSC, STE and initial documented rhythm. Results: The ATE(%, 95% confidence interval) of CAG in all OHCA patients for CPC 1-2 at 30 and 90 days was 3.11% (2.92-3.30) and 1.85% (1.74-1.95), and survival at 30 and 90 days was 6.25%(5.93-6.57) and 2.20%(1.88-2.52), respectively. The subgroup analysis of ATE for CPC 1-2 at 90 days was particularly lower in the no STE group, initial pulseless electrical activity (PEA) group and initial asystole group than in the STE group and initial ventricular fibrillation(VF) group (Figure). Conclusions: In the JAAM-OHCA registry, we used a counterfactual machine learning model to estimate the effect of CAG on OHCA.
Abstract 155: Intra-arrest Epinephrine Administration is Associated with Increased Myocardial Injury and Inflammation in a Novel Murine Model of Cardiac Arrest
Authors: Jason E Bloom, Daniel Donner, Waled Shihata, Aascha Brown, Tsin yee Tai, Gavin W Lambert, Po-Yin Chu, William Chan, Dion Stub, Bing Wang, David M Kaye
Journal: Circulation (2022)

Introduction: Epinephrine (EPI) is routinely administered in cardiac arrest resuscitation. Using a novel murine model of cardiac arrest, this study aims to assess the effects of epinephrine on myocardial inflammation and injury. Hypothesis: Intra-arrest epinephrine use is associated with increased myocardial injury, inflammation and fibrosis. Methods: A total of 56 mice were included in the study. Both cardiac arrest (CA) and sham (SHAM) groups received intravenous potassium chloride either as a bolus (CA) or slow infusion (SHAM), inducing ECG-confirmed asystole (CA only) for 4-minutes prior to delivery of intravenous epinephrine (250ul, 30ug/ml) or saline (250ul) and manual chest compressions (300BPM) for 4-minutes (Fig A). Mice were recovered for assessments at 24- or 72-hour timepoints. Results: Rates of successful ROSC (n=21(96%) vs. n=14(82%), P=0.18) and survival to recovery (n=11(50%) vs. n=12(71%),P=0.19) were similar in CA treated with (CA+EPI) and without (CA-Epi) EPI, respectively. Greater myocardial injury occurred in CA+EPI, compared to CA-Epi, with increased Hs-Troponin levels measured at 24- (26.0±0.9ng/mL vs. 9.4±5.3,P=0.015) and 72-hours (20.9±8.3ng/mL vs. 5.0±2.4,P=0.012) (Fig B). To examine mRNA expression in cardiac tissue, rt-PCR was performed. At 72-hours, CA+EPI, compared to CA-EPI, was associated with significantly increased expression of inflammatory (TNF-α, IL1β, IL10, F4-80 and CD68) and fibrotic (TGFβ, Col1 and Col3) genes. There was no difference between SHAM-EPI and SHAM+EPI at 72-hours (Fig C). Conclusion: In a mouse model of cardiac arrest, the use of epinephrine did not improve rates of ROSC and survival. However, epinephrine exposure was associated with increased biomarkers of myocardial injury, end-organ inflammation, and fibrosis. These findings underscore the need for further pre-clinical studies to assess alternate agents that confer protection to vital organs and improve rates of survival.
Abstract 15622: Hydro-Pneumopericardium Due to Esophageal-Pericardial Fistula: A Rare Complication of Esophageal Stent Migration
Authors: Suzanna Talento, Svenja Schneider, Waqas Ullah, Gregary D Marhefka
Journal: Circulation (2022)

Introduction: Esophageal-pericardial fistulas are rare complications of a variety of conditions ranging from benign esophageal disorders to iatrogenic etiologies such as radiofrequency catheter ablation. Here, we present a unique case of esophageal-pericardial fistula formation following esophageal stent migration in the setting of ulcerative esophagitis and benign esophageal stricture. Case Presentation: A 53-year-old woman with a history of ulcerative esophagitis and associated esophageal stricture was managed with esophageal stenting. Following stenting, her course was complicated by esophageal stent migration, resulting in severe dysphagia and multiple gastrointestinal bleeds requiring percutaneous endoscopic gastrostomy (PEG) tube placement. She presented with fatigue, melena, and dark output from her PEG tube and was hypotensive, tachycardic, and tachypneic. An echocardiogram (Figure 1A) showed hydro-pneumopericardium with cardiac tamponade physiology requiring emergent pericardiocentesis and aspirated fluid shown in Figure 1B. A subsequent computed tomography (CT) scan of the chest demonstrated a large complex pericardial effusion with air in the anterior pericardium, a large esophageal-pericardial fistula, and a moderate left hydropneumothorax (Figure 1C). Given the extent of her esophageal defect, the patient was taken for an esophagectomy with esophagostomy formation. Discussion: On review, we found only a few cases of hydro-pneumopericardium in the context of spontaneous pericardial herniation due to subcutaneous emphysema, radiofrequency ablation for atrial arrhythmias and esophagectomy for esophageal adenocarcinoma. However, there has been no report of esophageal-pericardial fistula due to esophageal stent migration. Conclusion: In an appropriate setting, clinicians should maintain a high index of suspicion for esophageal-pericardial fistulas, as delay in the management of these conditions could be fatal.
Abstract 15809: Ascending Late Onset Bacteremia Causing ICD Pocket Infection via a Lead-Associated Veno-Pocket Fistulous Tract
Authors: Edward R Horton, Syed M Zaidi, William Perucki, Anuj Basil, Edmond Cronin, Joshua M Cooper, Isaac R Whitman
Journal: Circulation (2022)

Case Presentation: A 51-year-old man with a history of non-ischemic cardiomyopathy, resolved line-associated Staph aureus bacteremia (SAB), and subsequent defibrillator (ICD) implant presented with sepsis. He was covered empirically with antibiotics and 4/4 blood cultures from admission grew MSSA. On exam, the patient’s pocket was non-tender, non-erythematous, and non-fluctuant, with a well-healed incision. A chest CT revealed multiple septic pulmonary emboli. ICD extraction was performed, exactly 580 days after last pocket entry. In the OR, the pocket drained copious pus and a distinct fistulous tract was noted along the lead, tracking to the pocket from the axillary vein ( Figure ). Full pocket debridement was performed, the entire system was extracted, and a drain was placed. The ICD lead tip culture grew MSSA; however, the pocket culture was negative. A source for the SAB was not determined. After completion of antibiotics and confirmatory negative blood cultures, a contralateral ICD was implanted. Discussion: A significant subset of CIED pocket infections present late (≥1 year from last pocket entry) and presume either indolent pocket infection descending to the bloodstream or, more likely, in the case of virulent bacteria like Staph aureus, ascending hematogenous spread to the device pocket. However, macroscopic evidence of this mechanism has not yet been demonstrated. The Figure grossly illustrates a presumed phenomenon - bacteria from the bloodstream forming a lead-associated fistulous tract to a previously sterile pocket, demonstrating proof-of-concept of a continuous environment between the pocket and bloodstream. This pathophysiology is central to established CIED guidelines on bacteremia, which emphasize the importance of early extraction and alternate-site re-implantation.